Benefits and Harms of Oral Anticoagulant Therapy in Chronic Kidney Disease: A Systematic Review and Meta-analysis

Jeffrey T Ha; Brendon L Neuen; Lap P Cheng; Min Jun; Tadashi Toyama; Martin P Gallagher; Meg J Jardine; Manish M Sood; Amit X Garg; Suetonia C Palmer; Patrick B Mark; David C Wheeler; Vivekanand Jha; Ben Freedman; David W Johnson; Vlado Perkovic; Sunil V Badve

doi:10.7326/M19-0087

Benefits and Harms of Oral Anticoagulant Therapy in Chronic Kidney Disease: A Systematic Review and Meta-analysis

Ann Intern Med. 2019 Aug 6;171(3):181-189. doi: 10.7326/M19-0087. Epub 2019 Jul 16.

Authors

Jeffrey T Ha¹, Brendon L Neuen², Lap P Cheng¹, Min Jun², Tadashi Toyama³, Martin P Gallagher⁴, Meg J Jardine⁴, Manish M Sood⁵, Amit X Garg⁶, Suetonia C Palmer⁷, Patrick B Mark⁸, David C Wheeler⁹, Vivekanand Jha¹⁰, Ben Freedman¹¹, David W Johnson¹², Vlado Perkovic², Sunil V Badve¹

Affiliations

¹ The George Institute for Global Health, UNSW Medicine, and St. George Hospital, Sydney, New South Wales, Australia (J.T.H., L.P.C., S.V.B.).
² The George Institute for Global Health, UNSW Medicine, Sydney, New South Wales, Australia (B.L.N., M.J., V.P.).
³ The George Institute for Global Health, UNSW Medicine, Sydney, New South Wales, Australia, and Kanazawa University, Kanazawa, Japan (T.T.).
⁴ The George Institute for Global Health, UNSW Medicine, and Concord Repatriation General Hospital, Sydney, New South Wales, Australia (M.P.G., M.J.J.).
⁵ Institute for Clinical Evaluative Sciences, Toronto, and Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada (M.M.S.).
⁶ Institute for Clinical Evaluative Sciences, Toronto, and London Health Sciences Centre and Western University, London, Ontario, Canada (A.X.G.).
⁷ University of Otago, Christchurch, New Zealand (S.C.P.).
⁸ Institute for Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (P.B.M.).
⁹ University College London, London, United Kingdom (D.C.W.).
¹⁰ The George Institute for Global Health, New Delhi, India, University of Oxford, Oxford, United Kingdom, and University of New South Wales, Sydney, New South Wales, Australia (V.J.).
¹¹ Concord Repatriation General Hospital and Heart Research Institute, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia (B.F.).
¹² Princess Alexandra Hospital, Translational Research Institute, and Australasian Kidney Trials Network, University of Queensland, Brisbane, Australia (D.W.J.).

PMID: 31307056
DOI: 10.7326/M19-0087

Abstract

Background: Effects of oral anticoagulation in chronic kidney disease (CKD) are uncertain.

Purpose: To evaluate the benefits and harms of vitamin K antagonists (VKAs) and non-vitamin K oral anticoagulants (NOACs) in adults with CKD stages 3 to 5, including those with dialysis-dependent end-stage kidney disease (ESKD).

Data sources: English-language searches of MEDLINE, EMBASE, and Cochrane databases (inception to February 2019); review bibliographies; and ClinicalTrials.gov (25 February 2019).

Study selection: Randomized controlled trials evaluating VKAs or NOACs for any indication in patients with CKD that reported efficacy or bleeding outcomes.

Data extraction: Two authors independently extracted data, assessed risk of bias, and rated certainty of evidence.

Data synthesis: Forty-five trials involving 34 082 participants who received anticoagulation for atrial fibrillation (AF) (11 trials), venous thromboembolism (VTE) (11 trials), thromboprophylaxis (6 trials), prevention of dialysis access thrombosis (8 trials), and cardiovascular disease other than AF (9 trials) were included. All but the 8 trials involving patients with ESKD excluded participants with creatinine clearance less than 20 mL/min or estimated glomerular filtration rate less than 15 mL/min/1.73 m2. In AF, compared with VKAs, NOACs reduced risks for stroke or systemic embolism (risk ratio [RR], 0.79 [95% CI, 0.66 to 0.93]; high-certainty evidence) and hemorrhagic stroke (RR, 0.48 [CI, 0.30 to 0.76]; moderate-certainty evidence). Compared with VKAs, the effects of NOACs on recurrent VTE or VTE-related death were uncertain (RR, 0.72 [CI, 0.44 to 1.17]; low-certainty evidence). In all trials combined, NOACs seemingly reduced major bleeding risk compared with VKAs (RR, 0.75 [CI, 0.56 to 1.01]; low-certainty evidence).

Limitation: Scant evidence for advanced CKD or ESKD; data mostly from subgroups of large trials.

Conclusion: In early-stage CKD, NOACs had a benefit-risk profile superior to that of VKAs. For advanced CKD or ESKD, there was insufficient evidence to establish benefits or harms of VKAs or NOACs.

Primary funding source: None. (PROSPERO: CRD42017079709).

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Administration, Oral
Anticoagulants / adverse effects*
Anticoagulants / therapeutic use*
Atrial Fibrillation / drug therapy
Cardiovascular Diseases / prevention & control
Glomerular Filtration Rate
Humans
Kidney Failure, Chronic / drug therapy*
Randomized Controlled Trials as Topic
Renal Replacement Therapy
Thromboembolism / prevention & control

Substances

Anticoagulants